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We present an 82-year-old male patient who underwent laparoscopic abdominal perineal rectal amputation and D3 lymph node dissection, including left inguinal lymph node dissection for anal canal carcinoma. Left inguinal lymph node metastasis was positive, and pT1bN2aM0, pStage Ⅲa was the final pathological diagnosis. He underwent 8 courses of capecitabine plus oxaliplatin therapy as adjuvant chemotherapy. He was examined without recurrence for 5 years postoperatively. However, he awared a perineal subcutaneous tumor and was transferred to our hospital for further examination and treatment 6 years postoperatively. Recurrence after anal canal carcinoma surgery was diagnosed based on a needle biopsy, and perineal subcutaneous tumor resection was performed. This is a rare case of late postoperative recurrence of anal canal carcinoma, which was detected due to a perineal subcutaneous tumor 6 years after surgery for anal canal carcinoma.

The patient was a 75-year-old man who had undergone potentially curative surgery for Stage Ⅲb rectal cancer followed by resection of liver metastases. Two years after the resection of liver metastases, lung and remnant liver metastases were found. He received chemotherapy for unresectable metastatic tumors. Based on the findings of molecular and pathological examinations(RAS: wild type; BRAF: wild type; MSI: negative; HER2: negative), the following chemotherapy regimens were administered: first-line, FOLFIRI plus panitumumab(PANI); second-line, mFOLFOX6; third-line, trifluridine/tipiracil; fourth- line, regorafenib. After fourth-line treatment, he was judged to have disease progression due to the increase in his lung and liver metastases and the elevation of tumor markers. All standard regimens were refractory, but the Eastern Cooperative Oncology Group performance status was zero and a liquid biopsy for RAS still showed wild type. Therefore, rechallenge therapy with anti-epidermal growth factor receptor(EGFR)drugs, cetuximab(CET)and irinotecan(IRI), was administered 13 months after the final course of FOLFIRI plus PANI treatment. After 4 courses of CET plus IRI, the size of the 2 metastatic tumors markedly decreased and his tumor marker levels normalized.

A 66-year-old man presenting with cStage Ⅲc rectal cancer underwent laparoscopic low anterior resection(D3 lymph node dissection and R0 resection)following neoadjuvant chemoradiotherapy(capecitabine, 45 Gy/25 Fr)and received adjuvant chemotherapy(CAPOX). A year after surgery, abdominal contrast-enhanced computed tomography revealed recurrence near the rectal anastomosis with prostate invasion. The patient underwent robot-assisted abdominoperineal resection alongside en bloc prostatectomy and vesico-urethral anastomosis after 12 courses of neoadjuvant chemotherapy(FOLFIRI and panitumumab). He exhibited a good postoperative course and was discharged on the 12th postoperative day. After 7 months of surgery, no recurrence was observe; and urinary incontinence seen immediately after surgery gradually improved.

Cancer-associated fibroblasts(CAFs)remodel the extracellular matrix(ECM)and shape the tumor microenvironment (TME), resulting in immune escape and the promotion of tumor metastasis. Using an orthotopic tumor model of colorectal cancers(CRCs)in mice, we demonstrated that the single-cell RNA sequencing of orthotopic rectal tumors identified a subpopulation of CAFs that modulate the immune response. In this review, we report that understanding the role of CAFs in the TME concerning tumor immunity may lead to future avenues for CAF-targeted therapy.

A 68-year-old woman with Parkinson's disease, who had previously undergone Roux-en-Y gastrojejunostomy for early gastric cancer, complained of wearing-off and troublesome dyskinesia that had progressed over 7-years. After the introduction of levodopa-carbidopa intestinal gel therapy (LCIG) by nasojejunal tube, she had a good clinical response. Percutaneous endoscopic gastrostomy with a jejunal extension tube was difficult in this case, due to lack of gastrostomy site and fibrous postoperative adhesion. We introduced LCIG by direct percutaneous endoscopic jejunostomy (D-PEJ) which offers a less invasive procedure to operative tube placement. The factors affecting the success of D-PEJ could interfere with transillumination, abdominal thickness and the location of other organs. We determined the optimum site of catheter insertion with the assistance of real-time 3D reconstruction CT-jejunography. She was discharged home on postoperative day 14 without any procedure-related complications. Real-time 3D reconstructive CT-jejunography guided D-PEJ is a useful method for a patient who benefit from LCIG with prior gastrojejunostomy.

Chemotherapy for elderly patients requires ingenuity in treatment to mitigate its high risk. Therefore, we investigated an upfront dose reduction in the first cycle of chemotherapy for unresectable/recurrent gastric cancers in patients over 80 years old. We examined 6 patients over 80 years old, who underwent S-1 plus L-OHP therapy(SOX)for unresectable/recurrent gastric cancer in our department between January 2020 and January 2021. There were no adverse events over Grade 3 in the upfront dose reduction group(U group), while 1 case(50.0%)in the normal dose group(N group)experienced an adverse event over Grade 3. Moreover, only the U group continued treatment for 4 or more courses, whereas none from the N group did. Partial response(PR)was achieved as a therapeutic effect in 3 patients of the U group. Only 2 cases of the U group advanced to the second-line regimen and both were able to transition to the third-line regimen. However, none were able to even transition to the second-line regimen in the N group. Therefore, it was suggested that by reducing the dose of chemotherapy from the first cycle for elderly patients over 80 years old, the incidence of adverse events can be kept low, which makes it possible to continue long-term chemotherapy.

An 80-year-old man underwent laparoscopic rectal high anterior resection with perineal dissemination for the management of RS rectal cancer. Following the diagnosis of RS rectal cancer with muc, pT4a, N3(14/15), M1c, P1, pStage Ⅳc, RAS/BRAF: wild type, treatment was initiated with mFOLFOX6 plus panitumumab(Pmab). Laboratory examination on admission revealed mild renal dysfunction(Cr 1.45 mg/dL). The patient became confused on day 3 of chemotherapy(JCS Ⅲ-200). Furthermore, laboratory findings revealed a serum ammonia level of 338μg/dL. He was diagnosed with 5-FU- induced hyperammonemic encephalopathy. Discontinuation of high-dose 5-FU and branched-chain amino acid solutions improved his mental status and decreased serum ammonia levels. We switched his chemotherapy regime to CPT-11 plus Pmab, but it was discontinued after 1 course on his request.

A 50s old woman admitted to our hospital with anal pain, who was diagnosed as rectal gastrointestinal stromal tumor (GIST). After neoadjuvant therapy with imatinib mesylate for 6 months, the tumor reduced by 75% from its original size and anus preserving operation(low anterior resection)was performed. After operation adjuvant therapy with imatinib mesylate was performed for 2 years and 6 months. The patient is alive without recurrence 5 years after surgery. It is suggested that neoadjuvant therapy with imatinib mesylate is useful and safety for large rectal GIST, from the standpoint of anal preservation.

Case 1: A 73-year-old man underwent total gastrectomy for residual gastric cancer, and final pathological diagnosis was pStage ⅠB. Adjuvant chemotherapy was not performed. CT findings showed multiple liver metastasis 16 months after procedure. S-1 and CDDP were administered for 28 months. Although chemotherapy regimen was changed to S-1, paclitaxel plus ramucirumab, nivolumab, irinotecan and S-1 plus oxaliplatin(SOX)after progression, he died 73 months after operation, and 57 months after recurrence. Case 2: A 72-year-old man was pointed out swelling of gastric lymph nodes in CT imaging. He was diagnosed as advanced gastric cancer with para-aortic lymph node metastasis by followed examination. S- 1 plus CDDP was administrated for 30 months. S-1 and SOX were administered after progressive findings, but he died 48 months after diagnosis. We report 2 cases of recurrent and advanced gastric cancer with long-term survival because of successful chemotherapy.

A 69-year-old woman, who complained of appetite loss, was diagnosed with Type 3 gastric cancer, and a biopsy resulted in the diagnosis of adenocarcinoma(tub2-por), Group 5. Abdominal computed tomography (CT) revealed bulky metastatic lymph nodes around the stomach and the aorta. The diagnosis was cT4a, cN2, cM1(LYM), cStage ⅣB, and SP therapy(a combination of S-1 and cisplatin) was immediately administered. On the completion of 3 courses of SP therapy, both the primary tumor and lymph nodes markedly decreased in size. Based on this finding, D2 total gastrectomy, No. 16 lymph node dissection, splenectomy, and right adrenal tumor resection were performed. Histopathology showed no residual tumor cells in the stomach or lymph nodes. Postoperatively, she received S-1 therapy, which was discontinued on completion of the first course due to its side effects. She survived for over 7 years postoperatively without receiving chemotherapy and showed no recurrence.

A 63-year-old asymptomatic woman was diagnosed with multiple liver tumors and a left pulmonary tumor by CT. Colonoscopy( CS)showed a Type 2, quarter circular tumor on Rb. The diagnosis was cT3N1aM1b(H3, PUL1), cStage Ⅳb rectal cancer. She was administered 8 courses of induction-adjuvant chemotherapy with CAPOX and bevacizumab(BEV). After the chemotherapy, CT and CS revealed shrinkage(up to 50%)of the metastatic liver tumor and primary tumor, and decreasing tumor marker levels. Laparoscopic abdominoperineal resection and partial hepatectomy(S5/6, S8)were performed. After the operation, she was administered 2 courses of chemotherapy with UFT and LV, after which thoracoscopy-assisted upper lobectomy of the left lung was performed. Currently, at 1 and a half years after treatment, no recurrence has been observed, and she is being followed up as an outpatient.

Currently, the immunotherapy approved for gastric cancer is immune checkpoint blockade( ICB) therapy. The effects of ICB depend on the T cell-mediated immune response elicited at the cancer site. Based on the results of previous clinical trials, it is clear that an enhanced immune response to cancer improves prognosis. Thus, the development of biomarkers to predict local immune responses may increase the significance of future immunotherapy for gastric cancer. Biomarker research has clearly progressed with the rapid development of genetic analysis technologies, enabling the analysis of data from clinical trials. Not only the molecular biomarkers known to date for ICB biomarkers, but immune cells that influence ICB therapy are also reviewed in this article.

A 24-year-old man, who had been treated for 3 years as Asperger syndrome in adolescence due to behavioral disturbances, lack of social awareness and inability to socialize, was referred to our hospital shortly after tremors developed. On the basis of clinical features, laboratory findings and the brain MRI, a diagnosis of Wilson's disease (WD) was made. WD was further confirmed by genetic testing (the mutation of ATP7B gene). He was started with trientine hydrochloride 500 mg/day, and after 1 year of follow-up, his psychiatric symptoms have improved. Since psychiatric symptoms may precede the neurological symptoms, the possibility of WD should be always considered in the differential diagnosis of psychiatric disorders in young adults.

A 40-year-old woman was admitted to our hospital with the chief complaint of miction pain. MRI showed fundal wall thickening of the bladder in contact with the appendix. Under cystoscopy, redness of the mucous membrane was found in the posterior wall of the bladder. Therefore, laparo-appendectomy with partial cystectomy was performed. Microscopically, adenocarcinoma cells were observed in the lumen of the appendix, invading the wall of the urinary bladder at the fundus of the appendix. We performed laparo-ileocecal resection for a regional lymphadenectomy. Thus, the patient was diagnosed with adenocarcinoma of the appendix[V, type 3, 16×7 mm, tub2, pT4b(SI, urinary bladder), int, INF b, ly0, v0, pN0, cM0, pStage Ⅱ]. The patient has been receiving adjuvant chemotherapy using capecitabine for 6 months. There was no evidence of recurrence after 9 months of follow-up.

A 46-year-old man underwent a medical check-up and gastrointestinal endoscopy, which revealed a brown lesion at the greater curvature of the gastric body. Biopsy was performed, and a gastric neuroendocrine tumor(NET)was diagnosed. The serum levels of gastrin and other tumor markers were not elevated. The preoperative diagnosis was Rindi type Ⅲ gastric NET, and laparoscopic distal gastrectomy with D1 plus lymph node dissection was performed. Histological examination showed that the resected specimen was positive for chromogranin A, CD56, and synaptophysin, which was consistent with the findings of NET. Even though the tumor diameter was only 3 mm, a metastatic #4d lymph node was found. This case suggests that Rindi type Ⅲ gastric NET has high malignant potential, and gastrectomy with lymph node dissection is necessary, regardless of tumor size.

There are many reports on the association between infiltrating immune cells andcancer prognosis. It is generally thought that cancer cells escape from the immune surveillance system in vivo. Cells associatedwith tumor immunosuppressive mechanisms include macrophages, regulatory T cells, bone marrow-derived immunosuppressive cells(MDSC), andneutrophils. These immunosuppressive cells enhance the production of TGF-b andIL -10 andthe expression of PDL-1 by cytokines producedby stromal cells such as cancer cells andfibroblasts, thereby inducing cytotoxic T cells lymphocytes(CTL). On the other hand, it has been proved that CD8+ T cells react in an antigen-specific manner even in advanced gastric cancer, suggesting the possibility that memory T cells, NK cells andNKT cells in gastric cancer tissues correlate with goodprognosis. Recently, it has been reportedthat the presence of follicular lymphoidstructure calledtertiary lymphoidstructure(TLS)in gastric cancer tissue is associatedwith favorable prognosis. Although immune responses are suppressedin gastric cancer tissues, the effectiveness of an immune checkpoint inhibitor(anti-PD-1 antibody)has been provedin 2017. The tumor-infiltrating immune cells is known as a predictive effect biomarker. As cancer genome research progresses, which type of immune response is induced is gradually being elucidated in near future. Thus, assessing the invasive morphology and function of various tumorinfiltrating immune cells is considered to be extremely important in Precision Medicine for gastric cancer.

A seminar titled "Implementation and evaluation of genetic testing of lifestyle-related disease genes" was held for pharmacists, medical clerks, and clerks of pharmacy insurance, with the aim of holding seminars led by pharmacists for the general public (including patients) in the future. The subject of the seminar was single nucleotide polymorphisms in obesity-related genes and alcohol metabolism-related genes. The purpose of the seminar was to contribute to the prevention of lifestyle-related diseases of the general public. We evaluated it by administering a questionnaire to the participants before and after the seminar. After the seminar, 55% of pharmacists answered that they would like to or would strongly like to participate in genetic testing (for lifestyle-related diseases and drug metabolism-related genes) of the general public. However, some participants did not wish to do so. A customer satisfaction (CS) analysis found that this was mainly because they did not want to know the results of genetic testing of others, which they felt should be private. Most (82%) of the pharmacists answered that assistance and advice was "very necessary" or "necessary" in the participation of genetic testing. These findings show that collaboration between pharmacies and universities will be important for future seminars to the general public.

The field of pharmacotherapy has advanced to use molecular targeted agents, and pharmacists are now encouraged to focus on pharmacogenomics. A seminar titled "Implementation and evaluation of genetic testing of lifestyle-related disease genes" was presented to students at the Faculty of Pharmaceutical Sciences, Hiroshima University, describing the pharmacogenomic role of single nucleotide polymorphisms in obesity-related genes and alcohol metabolism-related genes. The seminar topic was selected first because pharmaceutical students were already familiar with some of the content, and secondly because we believe that pharmacists should be informed about the prevention of lifestyle-related diseases using genetic testing. We evaluated the usefulness of this seminar by administering a questionnaire before and after the seminar to participating students. Several points requiring improvement were identified, although 82% of students stated that the seminar was "very useful" or "useful". We conclude that this educational seminar was useful to students of pharmaceutical sciences.

A 69-year-old man underwent surgery for pancreatic head cancer. During surgery, a few tubercles were found in the bursa omentalis, which were diagnosed pathologically as peritoneal dissemination. Curative resection was impossible, and exploratory laparotomy was completed. After surgery, 17 cycles of S-1/gemcitabine combination chemotherapy were administered for 1 year. Significant changes were not observed in the primary tumor on computed tomography (CT) scan, but the uptake of fluorodeoxyglucose (FDG) in the tumor decreased on positron emission tomography combined with CT(PET/CT), suggesting a decrease in tumor activity. Although imaging modalities could not identify distant or peritoneal metastases, levels of serological tumor markers increased at this time. Therefore, a second exploratory laparotomy was performed 13 months after the initial surgery. The nodules in the bursa omentalis had disappeared, and the patient underwent a pancreatoduodenectomy with common hepatic artery resection. Histopathological findings revealed mucinous carcinoma of the pancreas. The postoperative diagnosis was pT3, pN2, M0, Stage IVa.

The stenting strategy for portal vein stenosis in cases with unresectable hilar malignancies reduces portal hypertension and maintains portal vein blood flow. This not only improves quality of life, but also leads to aggressive therapy with anticancer agents. A 65-year-old woman presented with painless jaundice 8 months after left hemihepatectomy with lymph node dissection for intrahepatic cholangiocellular carcinoma. Seven months after biliary stenting for bile duct stenosis, progressing pancytopenia and ascites were noted. Imaging studies revealed portal vein stenosis by the tumor at the hepatic hilum. Percutaneous transhepatic portal vein stent placement was performed, and pancytopenia and ascites improved immediately thereafter. Chemotherapy for recurrence of intrahepatic cholangiocellular carcinoma at the hepatic hilum has been initiated, and the patient has been alive 15 months since.

A retrospective analysis of 263 patients with previously untreated squamous cell carcinoma of the tongue between 2000 and 2010 was performed. Those patients, who received preoperative chemotherapy, had a history of head and neck cancer or had previously received radiotherapy for the other disease, were excluded. All patients underwent a surgical procedure as a part of the initial treatment. Patients with close or microscopically involved margins of resection, INF (Infiltrative growth pattern) gamma or at least two involved nodes were classified as high risk patients. Postoperative radiotherapy (PORT) was undertaken for the high risk patients. After a median follow-up of 72 months, the 5-year overall survival and 5-year cause-specific survival were as follows: 79.1%, 85.0% in all stages, 82.7%, 91.2% in Stage I (n = 76), 86.7%, 89.0% in Stage II (n = 98), 71.5%, 78.6% in Stage III (n = 57), and 61.5%, 69.1% in Stage IV (n = 32). Patients without high risk features had significantly higher overall survival rate than those in the case of high risk patients, despite receiving no PORT. For high risk patients, PORT significantly improved the locoreginal control rate, but the overall survival rate did not improve.

Intravascular large B-cell lymphoma (IVLBCL) is a rare variant of extranodal malignant large B-cell lymphoma characterized by the selective growth of lymphoma cells within the vessels. It is well known that the diagnosis of IVLBCL is sometimes difficult because of heterogeneity of clinical symptoms and the lack of lymphadenopathy and mass formation. Recently, the usefulness of performing random skin biopsy on healthy-appearing skin in patients with suspected of IVLBCL has been reported. Herein, we review the clinicopathological features of consecutive four cases of IVLBCL and discuss the possible diagnostic strategy, including the usefulness of analyzing biopsy specimen from senile hemangioma, in patients with suspected of IVLBCL. One of 4 cases of IVLBCL was diagnosed by random skin biopsies, which were performed in three cases; however, the random skin biopsy specimens showed no atypical lymphocytes in two cases. Biopsy from senile hemangioma clearly revealed accumulation of atypical lymphoid cells within the dilated vessels of senile hemangioma in the remaining three cases, which led to an ultimate diagnosis of IVLBCL. The results of this study demonstrated that performance and analysis of skin biopsy on senile hemangioma in combination with random skin biopsy is useful for the diagnosis of IVLBCL. The performance of combination skin biopsies on cutaneous hemangioma and normal-appearing skin could facilitate and verify early detection of lymphoma cells in patients suspected of IVLBCL, leading to appropriate therapy and good prognosis.

Tailor-made treatment for lymphoma has been proposed, based on the information on prognostic on predictors or on molecular targets. This recent evolutions necessitated the collection of sufficient tissue samples for their preoperative evaluation. Since needle biopsy or needle aspiration cytology may not provide enough tissue for histo-pathologic diagnosis, incisional and excisional biopsies are commonly performed. In this study, we applied a handheld vacuum-assisted biopsy (VAB) system, as an alternative to the conventional incisional and excisional biopsies, to evaluate its feasibility in the biopsy -based diagnosis of malignant lymphoma. The subjects were nine patients with clinically suspected malignant lymphoma. All of them were correctly diagnosed with a diagnostic accuracy of 100%, and lymphoma sub-types could be defined according to the New WHO classification. There was no complication associated with the procedure. Lymph node biopsy for diagnosis of malignant lymphoma using this minimally invasive VAB technique allows a simple and safe collection of sufficient samples with good-quality, and promises to contribute to a precise molecular-based diagnosis.

In the present study, we tested three kinds of sleeping drugs, consisting mainly of triazolam, brotizolam, and flunitrazepam, to compare the drug efficacy of generic drugs with that of original drugs. After these drugs were administered orally to mice, drug efficacy was evaluated in terms of ambulation, onset time of sleep, and duration of sleep in the open field test. For all kinds of sleep-inducing drugs, the drug efficacy of most generic drugs is not necessarily equal to that of the original drug. The main reason for the difference appears to be due to differences in the rate of absorption of the main drug. Any other differences between an original drug and a generic drug are caused by drug additives, the crystal form of the main drug, the formulation, and so on. In this study, the formulation was not the reason for the differences because all of the drugs were pulverized in a mortar and had no special coating. The drug additives for all the drugs are listed and the drug efficacy compared. Unfortunately, the information was not sufficient to shed any light on the differences in drug efficacy. For effective drug therapy, more information on drug additives should be provided.

Purpose: To verify the usefulness of the Veris III system, which is said to be problematic in clinical applications for recording multifocal electroretinograms (mfERG) by an ophthalmologist., Methods: A test wave was input to the system and the data were analyzed using Veris Science software. The items tested were overlapping, spatial averaging, combination procedures, and emission properties of the cathode ray tube (CRT) monitor (B 4)., Results: Overlapping was not observed under the standard stimulus conditions. The data resulting from both spatial averaging and combination procedures coincided with the theoretical calculated data defined by both procedures. Analysis of the emission properties of the CRT monitor showed that it took 85 mu seconds from the beginning to the end of the bright emission., Conclusions: No clinical problems were found in the M-sequence program, the spatial averaging procedure, or the combination procedure using several test waves. It is necessary to pay attention to the configuration of pattern stimulation on the CRT monitor (B 4), because it has a very steep emission during a very short time.

Background: Magnetic resonance imaging (MRI) is useful in pathogenesis, diagnosis, and treatment., Case: A 70-year-old man. He noticed that the right side of his upper lid had swollen 3 weeks previously. No abnormal findings were recognized in visual acuity, intraocular pressure, anterior segment, lens, vitreous, or fundus. From MRI findings 10 days after his first visit, dermoid cyst, soft tissue tumor, and nodular fasciitis were suspected. Because MRI 2 months after the first visit showed a decrease in tumor size, soft tissue tumor was ruled out. Finally histopathological examination revealed nodular fasciitis, although the findings during the operation did not differentiate between dermoid cyst and nodular fasciitis., Conclusion: MRI at different intervals was useful for clinical diagnosis.

Objective: To evaluate the effect of clioquinol on the optic nerve and retina of rhesus monkeys by ophthalmoscopy, electrophysiology and histopathology., Methods: Clioquinol was given orally to 5 monkeys, gradually increasingly from 100 mg/kg/day up to 14 months(total dosage 227 g/kg). Ophthalmoscopy, erectroretinogram(ERG), visual evoked potential(VEP) and histopathological examination of enucleated eyeballs were done periodically up to 10 years., Results: The margin of the optic disc was not clear at the early stage, but the colour became atrophic at the late stage. VEP maximum amplitude decreased quickly at the early stage and the amplitude of ERG a and b waves and oscillatory potential decreased gradually. 37 months after the discontinuation of administration of VEP, ERG amplitude increased gradually. Swelling of axons and disorganization of the myelin sheath were noticed 2.5 months after beginning treatment. Swelling of the peripapillary nerve fiber layer was seen 5.5 months after beginning treatment. Karyorrhexis was seen in the inner layer of the retina after 12.5 months. Axonal swelling disappeared and the myelin sheath became reorganized 9 months after the discontinuation of treatment., Conclusions: Clioquinol produced an early decrease of electrophysiological function, but recovery of function was seen after discontinuation of treatment. The degeneration of axons and myelin sheath continued during treatment, and interruption of the degeneration was seen after discontinuation of treatment.

Background: We examined a family with fundus albipunctatus in which mutation of the retinol dehydrogenase 5(RDH 5) gene was suspected to be the cause of this disease., Case: An 8-year-old girl had diffuse multiple white dots in her fundus except for the macula. She had good central vision. The amplitude of her electroretinogram wave was low, but it recovered after three hours of dark adaptation. Dark adaptometry showed an elevated threshold for rod adaptation. No visual field loss was observed. A homozygous missense mutation was found in exon 5 of the RDH 5 gene that substituted histidine for arginine at codon 280(Arg 280 His). Her mother had a normal fundus but was heterozygous for the same mutation., Conclusion: A missense mutation of RDH 5(Arg 280 His) was found in a Japanese family with fundus albipunctatus.

Purpose: The prostate size and motivation to visit clinics were investigated in patients with prostate hyperplasia., Objects and Methods: One hundred ninety-five patients who had urinary symptoms and visited our outpatient clinic between September 1994 and October 1999 and 268 age-matched volunteers in Mitaka City who underwent a medical examination of the prostate in June 1997 were compared. International Prostate Symptom Score (IPSS), Quality Of Life Score (QOL score), residual urine volume, prostate volume and urinary flow rate were measured., Results: The prostate volume of the volunteers was 20-25 cm3 irrespective of the age. The prostate size of the outpatients was larger than that of the volunteers for every age group. IPSS and QOL score were significantly higher in the outpatients than in the volunteers. Diurnal urinary frequency and sense of residual urine contributed to the discrimination index of the two groups more significantly than the other scores. There was a significant correlation between prostate volume and residual urine volume. The score of weak urinary steam was inversely and significantly correlated with peak urinary flow rate., Conclusions: There was no age-related enlargement of the prostate gland. The prostate gland was significantly larger in the patients than in the volunteers even in those in their fifties. Urinary frequency and sense of residual urine are important factors for men to seek and receive medical care.

Purpose: In Mitaka city, mass screening for prostate cancer was conducted for 3 years from 1995 to 1997. Clinical stages were compared between patients found by screening and those diagnosed at our clinic during the same time. The significance of serum-free prostate specific antigen (PSA) in mass screening for prostate cancer was examined., Material and Methods: A prospective clinical trial was conducted on men aged 50 years or older. The primary examination consisted of taking the international prostate symptom score, quality of life score, PSA (Tandem-R) and digital rectal examination (DRE). If PSA was greater than 4.0 ng./ml and/or if DRE suggested cancer, transrectal ultrasound-guided sextant prostate biopsies were indicated., Results: Of the men screened, 23.2% (320/1375) had serum PSA greater than 4.0 ng./ml. and/or suspicious findings on DRE. Biopsy was performed in 199 of 320 (62.1%). Cancer was detected in 21 (1.5%, 21/1375). Prostate cancer was found in one case among 154 males (0.65%, 1/154) who were screened twice or more. The cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic (Wilcoxon's rank-sum test: p = 0.0047). Receiver operating characteristics analysis showed that the optimal free PSA-to-PSA ratio was 12%. Positive predictive value increased from 18% to 50% when free PSA-to-PSA ratio was combined with PSA., Conclusion: 1. Cancer detection rate was 1.5% in the mass screening in Mitaka City. 2. Cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic. 3. Free PSA determination might eliminate unnecessary biopsies in men with PSA above 4.0 ng./ml with minimal loss of cancer detection.

We present a case of familial juvenile gouty nephropathy which was associated with a right renal tumor that was found incidentally. The patient was a 27-year-old woman who initially presented with acute gouty arthritis at the age of twenty years. Her mother and her sister had been attacked with acute gouty arthritis in their early twenties. Progressive deterioration in the renal function was noted in the three family members who had experienced gouty attack. Her mother was maintained on hemodialysis. As image diagnoses could not rule out malignancy in her right renal tumor, in situ non-ischemic enucleation of the right renal tumor using a microwave tissue coagulator(Microtaze) and a renal biopsy were performed. The pathological diagnosis of the renal tumor was tubulopapillary adenoma, and the renal biopsy showed minimal change in the glomeruli and tubules. The post-operative course was uneventful. The serum creatinine and creatinine clearance before and three months after the operation were 2.4 mg/dl and 2.6 mg/dl, 36.7 ml/min and 32.5 ml/min, respectively. The renal biopsy findings that glomerular and tubular changes were minimal and there was no tissue precipitation of uric acid or sodium urate, and the fact that her renal function decreased progressively despite the treatment of hyperuricemia suggested strongly that renal function might have deteriorated due to unknown factors other than hyperuricemia.

Nootropics are proposed to serve as cognition enhancers. The underlying mechanism, however, is largely unknown. We have attempted to assess the intracellular signal transduction pathways mediating the action of nefiracetam, a nootropic agent, on neuronal Ca2+ channels and nicotinic ACh receptors. In NG108-15 cells, nefiracetam (1 microM) enhanced the activities of N/L-type Ca2+ channels without affecting T-type The nefiracetam action was mimicked by dibutyryl cAMP (1 mM), or blocked by pertussis toxin (PTX), indicating that PTX-sensitive inhibitory G-proteins and cAMP-dependent pathways mediate the drug action. Nefiracetam also exerted a dose-dependent biphasic effect on Torpedo nicotinic acetylcholine (nACh) receptors expressed in Xenopus oocytes, in which the drug induced a short-term depression of ACh-evoked currents at submicromolar concentrations (0.01-0.1 microM) and a long-term enhancement of the currents at micromolar concentrations (1-10 microM). The depression was caused by activation of PTX-sensitive G-protein-regulated cAMP-dependent protein kinase (PKA) with subsequent phosphorylation of the ACh receptors; in contrast, the enhancement was caused by activation of Ca(2+)-dependent protein kinase C (PKC) and the ensuing PKC phosphorylation of the receptors. It is concluded that nefiracetam interacts with PKA and PKC pathways, which may explain a cellular mechanism for the action of cognitive enhancers.

We investigated the relation between multifocal electroretinograms (M-ERGs) and artificial parafoveal scotoma. M-ERGs were recorded from normal subjects using a circular piece of black paper attached to a monitor. Lower response density around the 10 to 15 degree parafovea region was not observed up to 3 degree scotoma (visual angle), but was detected above 5 degree scotoma in field topography of M-ERGs. The shape of the scotoma in field topography was not circular but somewhat oval. The results from two cases of parafoveal retinal degeneration were in good accordance with this basic study in normal subjects. We proved that detection of parafoveal scotoma by M-ERG is limited in comparison with the results obtained by automated static perimetry.

Avulsion of ureter without renal injury is rarely caused by blunt trauma, only 28 cases having been reported in Japan. A 33-year-old male was admitted to our hospital 1 month after blunt abdominal trauma at work. He complained of left flank pain and macroscopic hematuria. Under the suspicion of renal or ureteral injury, drip infusion urography and abdominal computerized tomography revealed an extravasation from the left upper ureter and urinoma formation in the retroperitoneal cavity. In order to reduce the inflammation, the urinoma was drained. The retrograde pyelogram revealed complete obstruction at the left upper ureter, 20 cm from the left ureteral orifice. Urinary tract reconstruction, end-to-end ureteral anastomosis, was performed under the diagnosis of left ureteral avulsion. Drip infusion urography revealed normal ureteral healing without stricture formation at 2 years after reconstruction.

Ro 5-4864, a specific agonist of the peripheral-type benzodiazepine receptor (PBR), elicited convulsions 2.6 times more potently in EL mice (an animal model of epilepsy) than in DDY mice (control animal). A binding assay revealed a 50% higher density of [3H] Ro 5-4864 binding sites in the mitochondrial fraction (i.e., mitochondrial benzodiazepine receptors; MBR) of the brain tissues in EL mice as compared with DDY mice. On an elevated plus-maze, EL mice showed fear responses similar to those increased in DDY mice after PBR stimulation, suggesting a hyperfunction of MBR underlying the abnormal behaviors of EL mice. In fluorometric studies using NG108-15 cells, Ro 5-4864 depolarized mitochondrial membranes and, possibly as a consequence of this, raised intracellular Ca2+. Finally, we propose that MBR could be a major target of therapy for various neurological disorders, so drugs such as "mitochondrial membrane stabilizers" should be developed.

We evaluated the protective effect of a newly designed soft contact lens (SCL) on rabbit eyes. This SCL absorbs the ultraviolet B light of wavelengths between 280 nm and 320 nm. Three weeks after resecting the nictitating membrane, the rabbit corneas were covered either by the new SCL or a conventional SCL. The eyes were exposed to ultraviolet light from two 15 W lamps placed 20 cm anteriorly for 3 hours. Another three hours after the exposure, the cornea was examined first with a slitlamp biomicroscope after staining with fluorescein and then by histopathological means after enucleation. Six eyes wearing the new SCL showed moderate superficial punctate keratopathy. Six eyes wearing conventional SCL showed severe superficial keratopathy or corneal erosion. These findings were in good agreement with the histopathological findings. The new ultraviolet-filtering SCL was thus effective in protecting the rabbit cornea under our experimental conditions.

We report a 63-year-old male patient with purpura nephritis, which appeared 7 days after extracorporeal shock wave lithotripsy (ESWL). He was referred to our clinic because of a petechial rash on both lower extremities, pretibial edema and massive proteinuria. Urinalysis showed proteinuria and hematuria and some hyaline casts. A 24-hour urine sample contained 5.0 g of protein. Renal function on admission was decreased: serum creatinine was 1.5 mg/dl and creatinine clearance, 21 ml/min. Immunoserological tests demonstrated an increase in serum IgA (424.3 mg/dl). A skin biopsy revealed leukocytoclastic vasculitis. A renal biopsy showed endocapillary proliferation in a diffuse, but segmental fashion. However, no crescent formation was seen. Immunofluorescence microscopy disclosed mesangial staining for IgA and C3. Electron microscopy demonstrated severe injury to endothelial and epithelial cells: detachment of endothelial and epithelial cells, foot process effacement and macrophage infiltration. Electron-dense deposits were observed in the subendothelial and paramesangial areas. Because renal function was deteriorating rapidly, methylprednisolone pulse therapy and immunosuppressive treatment were implemented. Treatment was effective and the patient's renal function and proteinuria improved remarkably. The electron microscopic findings in this case of purpura nephritis seemed to be more severe than usual, suggesting that ESWL may aggravate glomerular damage.

Purpose: To evaluate the usefulness of the CT guided percutaneous microwave tumor coagulation (PMTC) therapy for local recurrence of rectal cancer., Materials and Methods: The CT guided PMTC was performed for two patients with local recurrence of rectal cancer. Maximum axial diameter of the tumor was 30 mm on CT images. With patients in the prone position on the CT table, a 14-gauge needle-electrode was used to penetrate the tumor under epidural and local anesthesia. PMTC was performed with an output of 60 watts for 60 seconds at a time. Effects of the PMTC were evaluated by CT images obtained three months after the therapy., Results: In both cases, there was no evidence of tumor growth on the CT images. Clinical symptoms disappeared soon after the therapy, and no major complication was observed., Conclusion: The CT guided PMTC therapy was useful for local recurrence of rectal cancer.

The case of a twenty-year-old male with orbital chondrosarcoma is reported. He visited National Defense Medical College Hospital because of reduced vision in the right eye since two months previously. His corrected visual acuity was 8/20 in the right eye and 20/20 in the left eye. Fifteen degrees lateral displacement of the right globe and limitation of right ocular movement were recognized. Right fundus examination revealed optic disc edema and protuberant nasal fundus. Orbital computed tomography (CT) demonstrated a high density area between the inner part of the right orbit and the ethmoid sinus. Magnetic resonance imaging (MRI) showed a smoothly outlined and low intensity (T1) space occupying lesion. This lesion was irregularly enhanced by gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). This orbital tumor was removed by an anterior approach. Histopathological examination revealed well-differentiated chondrosarcoma (grade 1) as determined by small prominent chondromatous cell projection into the collagen fibrous stroma, and existence of binucleate cells in the hypercellular region. After the operation the disc edema disappeared and his corrected right visual acuity improved to 20/20.

A case of optic neuropathy after postoperative radiation therapy is reported. A 69-year-old woman had a partial resection of a pituitary adenoma in 1990 and was treated with 45Gy of irradiation to the postoperative pituitary lesion for one month. Seven months later she had sudden right visual field loss. Goldmann perimetry examination revealed remarked visual field defect in her right eye with visual acuity of 1.0. The right relative afferent pupillary defect was positive. The value of critical flicker fusion for her right eye was reduced and the amplitude of steady-state pattern-reversal visually evoked cortical potential was significantly less for the right monocular stimulation than that for the fellow eye stimulation, but Ganzfeld electroretinograms were normal for both eyes. Magnetic resonance imaging using Gadolinium-diethylene triaminepenta-acetic acid revealed enhancement on the right optic nerve, which had not been recognized immediately after the radiation therapy, without any suggestion of right optic nerve compression by the residual pituitary adenoma.

To introduce the proper voiding modality to patients with myelodysplasty, urethral opening pressure (UOP), an intravesical pressure just at the beginning urine flows out beyond the external urethral sphincter, was measured in 63 myelodysplastic patients. Among 45 renal units with any morphological or functional changes at the first UOP measurement, 37 units (82.2%) were included in the high UOP group (> or = 35 cmH2O). And among 41 ureters with VUR of more than grade 2, 32 (78.0%) were in the high UOP group. In addition, deformity of the urinary bladder was observed in 36 patients, and 26 (72.2%) of these bladders showed high UOP values. Therefore, all the patients could be divided into two groups: high UOP group (> or = 35 cmH2O, 28 cases) and low UOP group (< 35 cmH2O, 35 cases). Twenty-three patients (82.1%) with high UOP values had been mainly treated with clean intermittent catheterization (CIC). In contrast, 24 patients (68.6%) with low UOP values had been allowed to urinate by Credè' or Valsalva's method. In the followup study for 40 to 44 months, patients in the CIC group obtained good prognosis as for morphological or functional changes of the urinary tract. On the other hand, patients in the Credè' or Valsalva's method group showed a significantly higher deterioration rate in the high UOP group (80.0%) than that in the low UOP group (9.1%) (p < 0.005). From these results, hopely that in myelodysplastic patients with the underactive detrusor, CIC may be introduced for low pressure voiding to those who show high UOP values as early as possible. On the other hand, those who show low UOP values may be managed with Credè' or Valsalva's method as well as CIC. Thus, UOP is considered a possible prognostic factor for the morphological and functional changes of the urinary tract, which may be a useful parameter in decision of voiding modalities in myelodysplastic patients.

Augmentation cystoplasty is evolving into a common method of surgical treatment for a low capacity and/or low compliance neurogenic bladder. Although an increasing number of successful results have been recently reported, the operative indication of augmentation cystoplasty is yet to be established. Herein, we report two cases of neurogenic bladder due to spina bifida which required abandonment of augmentation cystoplasty. The first case was in a 23-year-old female with a severely deformed bladder and right vesicoureteral reflux (VUR). She refused to undergo ileocystoplasty because we could not assure her of postoperative conception which she eagerly anticipated. The second case was in a 19-year-old male with a severely deformed bladder and right VUR. He experienced recurrent episodes of ventriculoperitoneal shunt (V-P shunt) difficulty which required exchanging the shunt tube each time, and each exchange proved to be very difficult or nearly impossible. Based on lengthy neurosurgical consultation, we came to the conclusion that ileocystoplasty was not a preferable treatment of choice for the correction of his disease due to the possibility of V-P shunt infection, which could be fatal. Alternatively, both cases were treated with Cohen's ureteral reimplantation, which resulted in the recurrence of VUR. These cases presented still unresolved issues concerning the operative indication of augmentation cystoplasty in spina bifida patients.

A series of 32 patients with spina bifida, representing 50 renal units with vesicoureteral reflux (VUR), was treated with antireflux operation. All but one patient underwent ureteral reimplantation with Cohen's technique. Another patient was treated with bilateral Politano-Leadbetter's technique. The overall success rates were 92.0% by renal unit and 87.5% by case, with a mean follow-up period of 42.5 months. These results were comparable to those in the recent literature. Failure included recurrence of VUR in 3 patients. Another patient who had undergone unilateral reimplantation developed new occurrence of reflux in the contralateral ureter. Possible masking of contralateral VUR should be taken into consideration in patients with unilateral high grade VUR. We also emphasize the importance of continuing clean intermittent catheterization in a proper manner to be free of VUR postoperatively.

Urinary managements of 332 stroke patients in the chronic phase were performed at Bobath hospital. Cerebrovascular accidents (CVA) were caused by cerebral infarction in 178 (53.6%), intracerebral hemorrhage in 123 (37.1%) and subarachnoid hemorrhage in 31 (9.3%). Voluntary urination appeared in 124 patients before treatment, however in 29 of them occasional incontinence were observed. One hundred forty-three patients used diapers and 64 were controlled by indwelling catheters. The remaining one patient was treated by intermittent catheterization. Sixty-two patients who seemed to have communicative abilities in daily living were assessed with regard to their cerebrovascular dementia by Hasegawa's Dementia Rating Scale. After treatment 235 patients (70.8%) were able to urinate voluntarily, and only 15 of them remained incontinent and could use small pads successfully. TURP was effective for the stroke patients with benign prostatic hypertrophy (BPH) or bladder neck sclerosis (BNS). Fifty-three patients (16.0%) with persistent urinary incontinence were managed by diapers or a system of condom drainage. Thirty-nine patients (11.7%) were kept dry with intermittent catheterization at home, and long-standing use of indwelling catheters were required in the remaining 5 patients (1.5%). These results indicate that the lower level of activity, mobility and mental state tended to prevent the stroke patients from improvement of urinary disorders.

We discuss the transurethral resection of the prostate (TUR-P) on 40 patients in the chronic stage of stroke, all of whom were refractory to conservative managements of urinary disturbance. All patients, between 35 and 89 years old (mean: 52.6 years), had only one episode of stroke and were diagnosed as benign prostatic hypertrophy or bladder neck contracture that appeared to cause urinary disturbance in these patients. At six months after TUR-P, all except for one patient, who needed an indwelling catheter due to a reinfarction, were catheter free. Of these cases 36 (92%) obtained independent micturition and did not develop urinary incontinence except transiently postoperatively. Two cases with impaired mobility and one case with progressive senile dementia required helpmates and/or a commode and so forth postoperatively. It is concluded that in chronic stroke patients TUR-P is recommended for those with benign prostatic hypertrophy or bladder neck contracture.

To investigate the linearity and nonlinearity of both pattern electroretinogram (P-ERG) and pattern visually evoked cortical potential (P-VECP), a checkerboard pattern was presented to normal subjects with the reversal rate of transient and steady-state condition. Using a personal computer (BASIC) system, we made simulated waves (linear model) at 3 to 15 rev/s stimuli summated from an original wave evoked at 1 rev/s stimulation. Both simulated P-ERGs and P-VECPs were found to be different from the original ones, and the nonlinear component, which was interpreted as the difference between the original and simulated waves, was thought to increase with the increment of pattern reversal rate. However the 2 nd harmonic component of the original wave drastically decreased at above 7.5 rev/s stimulation. Thus, it is concluded that the nonlinearity of both P-ERG and P-VECP does not correlate with those 2 nd harmonic components.

A total of 154 stroke patients, 96 males and 58 females, were analyzed to establish the micturitional modality according to the type of detrusor function and the level of activities of daily living (ADL). All patients had only one episode of stroke attack and were checked at least one month after the onset. Localization of cerebral lesion in each patient was evaluated by neurological findings and cerebral angiography in addition to computed tomography of the brain. In the patient groups classified according to the type of detrusor function, micturitional modality was established in 50% of the patients with the underactive type, 70% of those with the overactive type and in 88% of those with normal function. This suggests that the overactive and normal type of detrusor function may not affect establishment of micturitional modality. On the other hand, when classified according to the level of ADL, none established micturitional modality in patients with poor ADL. By contrast, in the patients on higher levels of ADL who were able to transfer themselves from or to a wheel-chair without any assistance it was established in 75%, and in those who were able to gait with or without a brace upon discharged from the hospital, in 91%. It is concluded that establishment of micturitional modality in stroke patients is closely related to the level of ADL or function of lower extremities, but not to localization of the brain lesion.

We managed 246 patients with bladder dysfunction due to the first stroke in our hospital between January, 1983 and December, 1988. Of these 221 were in the chronic stage of stroke. A total of 213 patients were evaluated for types of bladder dysfunction by cystometry. We examined the relation between hemiplegic side and type of dysfunction or micturition activity, but obtained no significant relationship. Establishment of voluntary voiding pattern was considered to depend on the improvement of daily life activities. The catheter-free rate was 89.4%, while 10.6% of the patients, who could not receive sufficient nursing care or had severe medical problems, were obliged to keep an indwelling catheter. We conclude that establishment of a bladder retraining program is necessary not only medically but socially for improvement of quality of life in stroke patients.